The present invention relates to a process for preparing secondary amine N-oxide radicals by oxidizing the corresponding secondary amines.
Secondary amine N-oxide radicals, referred to hereinbelow as nitroxides, are free radicals containing an unpaired electron. These nitroxide radicals may be used as stabilizers for organic polymers, in particular to inhibit the thermal and light-mediated degradation of polyolefins (U.S. Pat. No. 3,431,233) and of PVC (U.S. Pat. No. 3,547,874). They are also used as spin labels for studying biological compounds and as free-radical polymerization regulators (Georges, M. K. et al. Macromolecules 1993, 26, 2987).
The main methods for preparing nitroxides are the oxidation of hydroxylamines and the oxidation of secondary amines, this second method being the one which is most commonly used industrially.
The methods for obtaining nitroxide radicals by oxidizing the corresponding secondary amines have been widely described.
Among these methods, mention will be made of those which use aqueous hydrogen peroxide solution in the presence of catalysts such as phosphotungstic acid (Brixc3xa9re R. et al., Bulletin de la Socixc3xa9txc3xa9 Chimique de France, 1965, pages 3273-3282), alkaline-earth metal salts (EP 0 574 607), NaHCO3 or Na2CO3 (Levina et al., Dokl. Akad. Nauk. SSSR 1981, 261(1), 109-110), EDTA combined with WO4Na2 (Zakizewski J., J. Prakt. Chem. 1985, 327(6), 1011-1014).
In all these methods, the oxidation reaction takes place in water or a water/alcohol mixture at temperatures of between 60 and 100xc2x0 C.
Although they use an inexpensive oxidizing agentxe2x80x94H202 xe2x80x94these methods are applicable only to amine/nitroxide couples that are sufficiently water-soluble. They also have drawbacks residing especially in long reaction times and in the impossibility of recycling the catalytic system, thus making it necessary to wash the product and treat the effluents before removing them.
In addition, these methods are not general since the temperatures used, generally high, make it difficult, if not impossible, to isolate certain nitroxides that are readily overoxidizable.
Other methods for oxidizing secondary amines to nitroxides have been proposed.
Thus, patent U.S. Pat. No. 4,665,185 discloses a process for oxidizing cyclic secondary amine, which consists in reacting said amine in an inert organic solvent, with an organic hydroperoxide such as tert-butyl hydroperoxide, in the presence of catalytic amounts of a metal carbonyl (Mo(CO)6), a metal oxide (MoO3), a metal acetylacetonate or a metal alkoxide (Ti(OiPr)4), the metal of which belongs to one of the groups IVB, VB, VIB, VIB and VIII of the Periodic Table, at a temperature ranging from 0xc2x0 C. to 200xc2x0 C.
The reaction times are shorter, but the problem of recovering the catalyst still remains. The products must be purified and the effluents treated.
Another method for oxidizing secondary amine consists in reacting said secondary amine with dimethyldioxirane (DMD) in the absence of catalysts (U.S. Pat. No. 5 087 752).
DMD, which is not commercially available, is prepared by oxidizing acetone either with Oxone(copyright) which is a potassium monoperoxysulsulfate, or more rarely with Caro""s acid which is an H2SO4/H2SO5 mixture.
This powerful oxidizing agent gives high yields of nitroxides. However, its highly explosive nature makes its preparation very random and is unacceptable for industrial use.
Furthermore, to obtain DMD, it is necessary to use the Oxone(copyright) in excess in basic medium, which generates a large amount of sulfate as effluent.
Perbenzoic acids such as meta-chloroperbenzoic acid (Journal of American Chemical Society, 1967, 89(12) 3055-3056) or para-nitropebenzoic acid (Rassat A. et al. Bulletin de la Socixc3xa9txc3xa9 Chimique de France, 1965, 3283-3290) dissolved in organic solvents such as methylene chloride, allow many secondary amines to be oxidized efficiently to nitroxides.
However, the cost and the benzoic acids they generate make them unsuitable for use on an industrial scale.
It has now been found that nitroxides can be obtained according to a process which avoids the abovementioned drawbacks, which consists in oxidizing secondary amines using aliphatic peracids in an organic solvent/water two-phase medium in which the aqueous phase is maintained at a pH ranging from 4 to 12.
One subject of the present invention is thus a process for preparing secondary amine N-oxide radicals (nitroxide radicals) from the corresponding secondary amines, characterized in that the following steps are carried out:
a/ the secondary amine is dissolved with a water-immiscible organic solvent, and water is then added,
b/ an amount of aliphatic peracid in a peracid/secondary amine molar ratio ranging from 1.5 to 2.5 and preferably ranging from 1.5 to 2, and an amount of an aqueous basic solution sufficient to give the aqueous phase or the two-phase medium a pH ranging from 4 to 12, are then added simultaneously and with vigorous stirring to the two-phase medium thus obtained, at a temperature of between xe2x88x9210xc2x0 C. and +40xc2x0 C., until conversion of the secondary amine is complete, and then
c/ the organic phase is recovered by simple separation of the phases by settling, and the nitroxide is isolated by evaporating the organic solvent under reduced pressure.
According to the present invention, the organic solvent must be water-immiscible, inert towards the reagents and products and must have good solvent power for the reagents and products obtained.
By way of illustration of such organic solvents which may be used according to the present invention, mention will be made of aliphatic or cycloaliphatic hydrocarbons such as pentane, hexane, heptane, decane, cyclohexane and cyclododecane; aromatic hydrocarbons such as benzene, toluene and xylenes; chlorinated hydrocarbons such as methylene chloride, 1,2-dichloroethane, chloroform and chlorobenzene; aliphatic acid esters such as ethyl acetate, ethyl propionate or a mixture of at least two of the abovementioned solvents.
By way of illustration of aliphatic peracids which may be used according to the present invention, mention will be made of peracetic acid, perpropionic acid and perbutanoic acid.
Peracetic acid or perpropionic acid will preferably be used.
The process of the present invention thus consists in dissolving, with stirring, the secondary amnine in water-immiscible organic solvent which is inert towards said secondary amine and the reagents used.
The amount of organic solvent used depends on the solubility of said secondary amine in said solvent.
This amount of organic solvent is not critical and may vary within a wide range. However, for economic reasons and out of concern for the environment, a person skilled in the art will make efforts to select an organic solvent (or a mixture of solvents) so as to use only minimum amounts to dissolve the secondary amine.
Water is added to the organic solution, with stirring, followed by simultaneous addition to the two-phase medium obtained, with vigorous stirring, of the aliphatic peracid, generally dissolved in the corresponding aliphatic acid, in a peracid/secondary amine molar ratio as defined above and a sufficient amount of an aqueous basic solution of a carbonate or hydrogen carbonate of an alkali metal or of an alkaline-earth metal so that the pH of the aqueous solution of the two-phase medium is maintained at a value ranging from 4 to 12 and preferably ranging from 5 to 9.
According to the present invention, an aqueous basic solution of an alkali metal carbonate or hydrogen carbonate will preferably be used.
By way of illustration of alkali metal carbonates or hydrogen carbonates which may be used according to the present invention, mention will be made of NaHCO3, KHC03, K2CO3 and Na2CO3.
Ammoniacal solutions may also be used.
The weight concentration of the aqueous solutions of alkali metal or alkaline-earth metal carbonates or hydrogen carbonates is set by the solubility limit of these species in water. Efforts will be made to use solutions that are as concentrated as possible.
The oxidation reaction of the secondary amine to nitroxide according to the scheme:
 greater than Nxe2x80x94H+{fraction (3/2)}RCO3Hxe2x86x92 greater than Nxe2x80x94O*+{fraction (3/2)}RCO2H+xc2xdH2O 
is carried out at a temperature ranging from xe2x88x9210xc2x0 C. to +40xc2x0 C. and preferably ranging from xe2x88x925xc2x0 C. to +30xc2x0 C. until the secondary amine is completely converted. The reaction progress may be monitored by analytical methods such as chemical assay of the peracid used according to methods known to those skilled in the art (assay with sulfite and with Ce4+) and gas chromatography.
The process is preferably performed at atmospheric pressure. Once the reaction is complete, the organic phase is recovered, generally by simple separation of the phases by settling. This organic phase may optionally be washed with a demineralized water and then dried.
The nitroxide formed is isolated by evaporating the organic solvent under reduced pressure. If necessary, the purity of the nitroxide may be improved by distillation under reduced pressure or by recrystallization. The nitroxides may be identified by elemental analysis, HPLC, IR, EPR and mass spectrometry (MS).
According to the process of the invention, the oxidation reaction of secondary amines to nitroxides has the advantage of being carried out with inexpensive, commercially available oxidizing agents, under mild conditions, quickly and in high yields.
In addition, the nitroxides obtained are easy to purify and the effluents (organic acid salts) may optionally be upgraded.
The process for oxidizing secondary amines to nitroxides according to the invention has the advantage or being applicable to secondary amines (or secondary polyamines) that are sterically hindered or to those containing a xe2x80x94CH xcex1 to the nitrogen atom.
In the present case, the expression xe2x80x9csterically hindered secondary aminesxe2x80x9d denotes amines which comprise at least one unit (A) as described below: 
in which Ra, Rb, Rc and Rd, which may be identical or different, represent a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 10, or Ra and Rb form with the carbon atom which bears them, or Rc and Rd form with the carbon atom which bears them, a cycloalkyl containing a number of carbon atoms ranging from 3 to 10 or a spiran, cholestane or androstane residue.
Thus, the oxidation process of the present invention makes it possible to oxidize into nitroxide sterically hindered secondary amines comprising at least one unit (A) or secondary amines containing at least one-CH a to the nitrogen atom, chosen from the compounds represented by the following formulae, in which Ra, Rb, Rc and Rd have the meanings mentioned above:
the compounds of formula (I): 
in which X represents a divalent radical chosen from the following radicals: 
in which Z represents a monovalent residue chosen from xe2x80x94CN, xe2x80x94NHR, xe2x80x94OR, xe2x80x94N=C(R)2 in which R represents a hydrogen atom, a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 10, a benzyl radical, a phenyl radical, xe2x80x94CN, xe2x80x94C(O)R1; C=Nxe2x80x94R1, C(OR1)2 in which R1 has the same meaning as R;
the compounds of formula (II): 
in which Y represents a divalent residue chosen from:
xe2x80x94OC(O)xe2x80x94(CR2R3)nxe2x80x94C(O) Oxe2x80x94,
xe2x80x94NHxe2x80x94(CR2R3)nNHxe2x80x94,
xe2x80x94NHC(O)xe2x80x94(CR2R3)nxe2x80x94C(O)NH,
xe2x80x94Sxe2x80x94, xe2x80x94Oxe2x80x94, R2 and R3, which may be identical or different, represent a hydrogen atom or a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 10, and n represents an integer ranging from 0 to 20;
the compounds of formula (III): 
in which R4 represents a hydrogen atom or a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 10, and R5 represents a hydrogen atom, xe2x80x94CH3, xe2x80x94C2H5, xe2x80x94CH2OH, xe2x80x94C(O)NH2, xe2x80x94OH or xe2x80x94CHO;
the compounds of formula (IV): 
in which R6 has the same meaning as R4 and R7 has the same meaning as R5 
the 1,1,3, 3-tetramethylpyrrolopoyridines of formula (V): 
and the 1,1,3,3-tetramethyl-2,3-dihydroisoindoles of formula (VI): 
in which R8 and R9 represent a hydrogen atom or a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 10;
the compounds of formula (VII): 
in which R10 and R11, which may be identical or different, represent a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 20, or a carboxyalkyl radical xe2x80x94(CH2)mCO2H in which m=1 to 20;
the compounds of formula (VIII): 
in which R12 represents a hydrogen atom, a linear or branched alkyl residue containing a number of carbon atoms ranging from 1 to 20, or a xe2x80x94C(O)NH2 radical, V=0; S, NH;
the compounds of formula (IX): 
in which R13 has the same meaning as R2 and W has the same meaning as V in formula (VIII):
the compounds of formula (X): 
in which R14, R15, R16, R17, R18 and R19, which may be identical or different, represent a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 20, a cycloalkyl radical containing at least 3 carbon atoms, a phenyl radical or a benzyl radical, or alternatively R14 and R15 form with the carbon atom which bears them, or alternatively R16 and R17 form with the carbon atom which bears them, a cycloalkyl containing a number of carbon atoms ranging from 3 to 10;
1,2,3,6-tetrahydro-2,2,6,6-tetramethylpyridine;
3,3-dimethyl-1-oxa-4-azaspiro[4.5]decane;
2,3,3,5,5-pentamethylmorpholine;
3,3,5,5-tetramethyl-2-methylenemorpholine;
N- (2,2,6,6-tetramethylpiperidyl-4) -xcex5-caprolactam;
4,4xe2x80x2-dimethylspiro(5xcex1-cholestane-3,2xe2x80x2-oxazolidine)
the compounds of formula (XI): 
with p=0 to 20;
the compounds of formula (XII): 
in which R20 and R21, which may be identical or different, represent a hydrogen atom, a linear, branched or cyclic alkyl radical containing a number of carbon atoms ranging from 1 to 10, an aryl radical, or an aralkyl radical, or alternatively R20 and R21 are linked together so as to form a ring including the carbon atom bearing said radicals R20 and R21, said ring containing a number of carbon atoms, including the carbon bearing the radicals R20 and R21, ranging from 3 to 8; R22 represents a linear or branched, saturated or unsaturated hydrocarbon-based radical which may comprise at least one ring, said radical containing a number of carbon atoms ranging from 1 to 30; R23 and R24, which may be identical or different, represent a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 20, a cycloalkyl, aryl, alkoxy, aryloxy, aralkyloxy, perfluoroalkyl, aralkyl, dialkyl or diarylamino, alkylarylamino or thioalkyl radical, or alternatively R23 and R24 may also be linked together so as to form a ring including a phosphorus atom, said heterocycle possibly containing a number of carbon atoms ranging from 2 to 4 and also possibly containing one or more oxygen, sulfur or nitrogen atoms;
the oxa-1-diaza-oxo-spirodecanes of formula (XIII): 
in which W1 and W2 are different and represent xe2x80x94C(O)xe2x80x94 or xe2x80x94NHxe2x80x94, R25 and R2 , which may be identical or different, represent a hydrogen atom, a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 18, a phenyl radical, a naphthyl radical or a phenylalkyl radical, R25 and R26 may also form, together and with the carbon atom which bears them, a cycloalkyl containing a number of carbon atoms ranging from 5 to 12 or a 2,2,6,6-tetramethylpiperidyl radical;
the secondary polyamines represented by the general formula (XIV): 
in which y=1 to 20, R27 represents an alkylene radical containing a number of carbon atoms ranging from 2 to 12 which may be interrupted with an xe2x80x94Oxe2x80x94 or xe2x80x94NR28xe2x80x94, R28 denoting a hydrogen atom, an alkyl radical containing a number of carbon atoms ranging from 1 to 12, a cycloalkyl radical, Q represents a radical xe2x80x94OR29, xe2x80x94NHR30 or xe2x80x94NR30R31 in which R29 represents a linear or branched alkyl radical containing a number of carbon atoms ranging from 1 to 12, a C3-C12 alkoxyalkyl radical, a cyclohexyl radical, a benzyl radical, a phenyl radical, a tolyl radical or a 2,2,6,6-tetrapiperidyl residue, R30 and R31 have the same meaning as R29, R30 and R31 may also form, together and with the nitrogen atom which bears them, a 5xe2x80x94, 6xe2x80x94 or 7-membered heterocyclic radical which may also contain an oxygen atom;
the secondary polyamine represented by formula (XV): 
in which z=1 to 200.
The present invention applies most particularly to the following secondary amines:
2,2,6,6-tetramethylpiperidine (formula (I) in which X=xe2x80x94CH2xe2x80x94 and Ra=Rb=Rc=Rd=xe2x80x94CH3),
4-hydroxy-2,2, 6,6-tetramethylpiperidine (formula (I) in which X= greater than CHZ with Z=OH and Ra=Rb=Rc=Rd=xe2x80x94CH3),
4-oxo-2,2,6,6-tetramethylpiperidine (formula (I) in which X=xe2x80x94C(O)xe2x80x94 and Ra=Rb=Rc=Rd=xe2x80x94CH3),
bis(2,2,6,6-tetramethylpiperidine) sebacate (formula (II) in which Y=xe2x80x94OC(O) (CH2)8 C(O)O and Ra=Rb=Rc=Rd=xe2x80x94CH3),
2,2,3,4,5,5-hexamethylpyrrolidine (formula (III) in which R4 =R5=xe2x80x94CH3 and Ra=Rb=Rc=Rd=xe2x80x94CH3),
2,2,4,5,5-pentamethyl-3-pyrrolidinylcarboxamide (formula (III) in which R4=xe2x80x94CH3, R5=xe2x80x94C(O)NH2 and Ra=Rb=Rc=Rd=xe2x80x94CH3),
2,2,4,5,5-pentamethyl-3-pyrrolinylcarboxamide formula (IV)
in which R6=xe2x80x94CH3, R7=xe2x80x94C(O)NH2 and Ra=Rb=Rc=Rd=xe2x80x94CH3),
the aminophosphates of formula (XII) in which R20=xe2x80x94H, R21=(CH3)3Cxe2x80x94, C6H11xe2x80x94, (CH3)2CHxe2x80x94, R22=(CH3)3Cxe2x80x94, C6H11, R23=R24=C2H5Oxe2x80x94, isopropoxy. Use will be made most particularly of diethyl 2,2-dimethyl-1-(1,1-dimethylamino)propylphosphonate, (R20=H, R21=R22=(CH3)3Cxe2x80x94, R23=R24=C2H5Oxe2x80x94),
2,2,7,7,9,9-hexamethyl-1-oxa-4,8-diaza-3-oxospiro-[4.5]decane (formula XIII) in which R25=R26=xe2x80x94CH3, W1=xe2x80x94NHxe2x80x94 and W2=xe2x80x94C(O)xe2x80x94),
2,2,4,4-tetramethyl-3,20-diaza-7-oxa-21-oxo-dispiro[5.1.11.2]heneicosane sold by the company Hoechst under the name Hostavin(copyright) N-20 (formula (XIII) in which R25 and R26 form a xe2x80x94(CH2)11xe2x80x94 ring, W1=C(O)xe2x80x94, W2=xe2x80x94NHxe2x80x94 and Ra=Rb=Rc=Rd=xe2x80x94CH3),
the polyamine of formula (XIV) in which R27=(CH2)6xe2x80x94, Q=NH-tC8H17 and Ra=Rb=Rc=Rd=CH3, sold by the company Ciba-Geigy under the name Chimassorb(copyright) 944.
The examples which follow illustrate the invention.
The secondary amines used are:
2,2,6,6-tetramethylpiperidine,
bis(2,2,6,6-tetramethylpiperidine) sebacate,
diethyl 2,2-dimethyl-1-(1,l-dimethyl-ethylamino)propylphosphonate, obtained according to a method described in international patent application Wo 96/24620,
Chimassorb(copyright) 944 with a weight-average molecular mass equal to about 3 000.
The nitroxides obtained are identified by gas chromatography (GC), their melting points and mass spectrometry (MS). The magnetic mass spectra were recorded on a Micromass Autospec(copyright) mass spectrometer equipped with an atmospheric pressure ionization (API) source. The mass spectra were obtained by accumulation of x spectra (x should correspond to the time for loop injection of 20 xcexcl directly into the API source).